17-28357364-G-GC

Variant names:

• chr17-28357364-G-GC
• rs11448856
• NM_015584.5:c.84dupG

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP6_Moderate

The NM_015584.5(POLDIP2):​c.84dupG​(p.Pro29AlafsTer41) variant causes a frameshift change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Benign (★).

• Frequency: Genomes: not found (cov: 33)
• Consequence: POLDIP2 NM_015584.5 frameshift
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 1.08

Genes affected

POLDIP2 (HGNC:23781): (DNA polymerase delta interacting protein 2) This gene encodes a protein that interacts with the DNA polymerase delta p50 subunit, as well as with proliferating cell nuclear antigen. The encoded protein maybe play a role in the ability of the replication fork to bypass DNA lesions. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Feb 2014]

ACMG classification

Verdict is Uncertain_significance. Variant got 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP6: Variant 17-28357364-G-GC is Benign according to our data. Variant chr17-28357364-G-GC is described in ClinVar as [Benign]. Clinvar id is 1249093.Status of the report is criteria_provided_single_submitter, 1 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
POLDIP2	NM_015584.5	c.84dupG	p.Pro29AlafsTer41	frameshift_variant	Exon 1 of 11	ENST00000540200.6	NP_056399.1
POLDIP2	NM_001290145.2	c.84dupG	p.Pro29AlafsTer41	frameshift_variant	Exon 1 of 11		NP_001277074.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
POLDIP2	ENST00000540200.6	c.84dupG	p.Pro29AlafsTer41	frameshift_variant	Exon 1 of 11	1	NM_015584.5	ENSP00000475924.2
POLDIP2	ENST00000618887.2	c.84dupG	p.Pro29AlafsTer41	frameshift_variant	Exon 1 of 11	2		ENSP00000477665.2

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD3 exomes AF: 1.00 AC: 162253 AN: 162262 Hom.: 81122 AF XY: 1.00 AC XY: 92254 AN XY: 92258

Gnomad AFR exome AF: 1.00

Gnomad AMR exome AF: 1.00

Gnomad ASJ exome AF: 1.00

Gnomad EAS exome AF: 1.00

Gnomad SAS exome AF: 1.00

Gnomad FIN exome AF: 1.00

Gnomad NFE exome AF: 1.00

Gnomad OTH exome AF: 1.00

GnomAD4 exome Cov.: 32

GnomAD4 genome Cov.: 33

Alfa AF: 1.00 Hom.: 5887

Asia WGS AF: 1.00 AC: 3478 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Jun 20, 2019

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

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Computational scores

Source: dbNSFP v4.3

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs11448856; hg19: chr17-26684390;